CONTENTS

• RBILD (respiratory bronchiolitis interstitial lung disease)
• DIP (desquamative interstitial pneumonia)
• Other smoking-related lung diseases covered in other chapters:
  • PLCH (pulmonary Langerhans cell histiocytosis) ➡️
  • AEP (acute eosinophilic pneumonia) ➡️
  • COPD (chronic obstructive pulmonary disease) ➡️
  • IPF (idiopathic pulmonary fibrosis) ➡️
  • CPFE (combined pulmonary fibrosis and emphysema) ➡️
• Questions & discussion

abbreviations used in the pulmonary section: 2

• ABPA: Allergic bronchopulmonary aspergillosis 📖
• AE-ILD: Acute exacerbation of ILD 📖
• AEP: Acute eosinophilic pneumonia 📖
• AFB: Acid Fast Bacilli
• AIP: Acute interstitial pneumonia (Hamman-Rich syndrome) 📖
• ANA: Antinuclear antibody 📖
• ANCA: Antineutrophil cytoplasmic antibodies 📖
• ARDS: Acute respiratory distress syndrome 📖
• ASS: Antisynthetase Syndrome 📖
• BAL: Bronchoalveolar lavage 📖
• BiPAP: Bilevel positive airway pressure 📖
• CEP: Chronic eosinophilic pneumonia 📖
• COP: Cryptogenic organizing pneumonia 📖
• CPAP: Continuous positive airway pressure 📖
• CPFE: Combined pulmonary fibrosis and emphysema 📖
• CTD-ILD: Connective tissue disease associated interstitial lung disease 📖
• CTEPH: Chronic thromboembolic pulmonary hypertension 📖
• DAD: Diffuse alveolar damage 📖
• DAH: Diffuse alveolar hemorrhage 📖
• DIP: Desquamative interstitial pneumonia 📖
• DLCO: Diffusing capacity for carbon monoxide 📖
• DRESS: Drug reaction with eosinophilia and systemic symptoms 📖
• EGPA: Eosinophilic granulomatosis with polyangiitis 📖
• FEV1: Forced expiratory volume in 1 second 📖
• FVC: Forced vital capacity 📖
• GGO: Ground glass opacity 📖
• GLILD: Granulomatous and lymphocytic interstitial lung disease 📖
• HFNC: High flow nasal cannula 📖
• HP: Hypersensitivity pneumonitis 📖
• IPAF: Interstitial pneumonia with autoimmune features 📖
• IPF: Idiopathic pulmonary fibrosis 📖
• IVIG: Intravenous immunoglobulin 📖
• LAM: Lymphangioleiomyomatosis 📖
• LIP: Lymphocytic interstitial pneumonia 📖
• MAC: Mycobacterium Avium complex 📖
• MCTD: Mixed connective tissue disease 📖
• NIV: Noninvasive ventilation (including CPAP or BiPAP) 📖
• NSIP: Nonspecific interstitial pneumonia 📖
• NTM: Non-tuberculous mycobacteria 📖
• OP: Organizing pneumonia 📖
• PAP: Pulmonary alveolar proteinosis 📖
• PE: Pulmonary embolism 📖
• PFT: Pulmonary function test 📖
• PLCH: Pulmonary Langerhans Cell Histiocytosis 📖
• PPFE: Pleuroparenchymal fibroelastosis 📖
• PPF: Progressive pulmonary fibrosis 📖
• PVOD/PCH Pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis 📖
• RB-ILD: Respiratory bronchiolitis-associated interstitial lung disease 📖
• RP-ILD: Rapidly progressive interstitial lung disease 📖
• TNF: tumor necrosis factor
• UIP: Usual Interstitial Pneumonia 📖

---

respiratory bronchiolitis interstitial lung disease (RB-ILD)

(back to contents)

---

---

basics of RB-ILD

• Nomenclature: (37055089)
  • RB (respiratory bronchiolitis) – refers to the pathologic finding of brown-pigmented macrophages in the respiratory bronchioles. This is present in virtually all lung biopsies of people who have a history of smoking.
  • RB-ILD (respiratory bronchiolitis interstitial lung disease) – refers to pathological findings combined with clinical and/or radiological evidence of interstitial lung disease.
• RB-ILD is a patchy, bronchiolocentric process. This is mirrored in the radiology of RB-ILD, which involves centrilobular nodules (since the bronchioles lie in the center of the pulmonary lobules).

---

epidemiology of RB-ILD

• >95% of patients are actively smoking.
• RB-ILD generally affects patients between 30-60 years old.
• Usually patients have >30 pack-years of tobacco exposure.
• RB-ILD is more common than DIP.

---

clinical findings in RB-ILD

symptoms

• RB-ILD is usually mild or asymptomatic.
• Symptoms may include:
  • Dyspnea.
  • Cough that may be productive (this may be difficult to differentiate from COPD).

physical examination

• Bilateral, end-inspiratory crackles are common. (Walker 2019)
• Wheezing may occur.
• Clubbing may be seen in ~20% of patients. (37055089)

---

radiology of RB-ILD

(Chest radiograph is generally normal).

CT scan findings

• Bronchial wall thickening has been reported in up to 90%. (37055089; 29222007) 
• Ill-defined centrilobular nodules are the classic finding of RB-ILD (~70%).
  • Usually upper lung predominant, but may also be diffuse.
  • The main differential diagnosis is hypersensitivity pneumonitis (HP). Differentiation of RB-ILD from HP is discussed here: 📖
• Mosaic attenuation, with patchy areas of reduced attenuation (~30%).
  • This usually isn't a prominent feature.
  • When present, this may be most obvious in the lower lobes. (Walker 2019)
• Mild ground glass opacities may also occur, which may be diffuse or patchy (66%).
• Centrilobular emphysema:
  • There is some suggestion that centrilobular nodules due to RB-ILD might evolve into centrilobular emphysema. (Walker 2019)
  • Centrilobular emphysema is present in two thirds of patients. (37055089) 

radiological differential diagnosis often focuses on:

• Differential diagnosis of centrilobular ground glass opacities: 📖
  • HP (hypersensitivity pneumonitis) – radiologically these entities may be very similar. 📖
  • Aspiration.
  • Entities seen in the context of pulmonary hypertension:
    • Cholesterol granulomas.
    • Pulmonary capillary hemangiomatosis.
• Differential diagnosis of bronchial wall thickening: 📖

---

diagnosis 

bronchoscopy

• Bronchoalveolar lavage (BAL):
  • Increased macrophages are expected (as are generally seen in people who smoke).
  • Bronchoalveolar lavage may help differentiate RB-ILD from HP (hypersensitivity pneumonitis). Lymphocytosis would suggest a diagnosis of HP, rather than RB-ILD.
• Transbronchial biopsy is not reliable, due to the patchy nature of the disease. (29222007)

diagnostic approach

• Diagnosis is generally based on a combination of:
  • (1) Smoking history.
  • (2) Radiological changes.
  • (3) Consideration of alternative diagnoses.
  • (4) Sometimes: bronchoscopy with bronchoalveolar lavage.
• Invasive diagnostic testing is often not required.
  • Centrilobular nodules and ground glass opacities should generally regress following smoking cessation. (26479130, 17135233) Thus, a diagnostic/therapeutic trial of smoking cessation could be a reasonable alternative to invasive diagnostic testing.
  • Bronchoalveolar lavage may be used to exclude hypersensitivity pneumonitis.
  • Tissue biopsy is usually not required. (26138798)

---

treatment & prognosis of RB-ILD

• Smoking cessation is the fundamental intervention.
• Many patients have comorbid COPD, which may be more amenable to therapy.
• RB-ILD is generally a benign and self-limited condition.
  • RB-ILD doesn't usually progress to severe fibrosis nor mortality.

---

desquamative interstitial pneumonia (DIP)

(back to contents)

---

---

basics of DIP

• Both RB-ILD and DIP involve infiltration of the lung tissue by macrophages.
• In some cases, RB-ILD and DIP might represent different stages of the same disease process. (Murray 2022) 
  • (#1) Initially, macrophages involve only the bronchioles (RB-ILD).
  • (#2) With more advanced disease, macrophage infiltration spreads further to involve the alveoli as well (DIP).
• DIP involves more diffuse infiltration of macrophages into alveolar parenchyma. This causes more significant physiological derangement – with potentially more serious clinical consequences.

---

epidemiology of DIP

• DIP is much less common than RB-ILD.
• Patients usually present in their 40s-60s. (29222007)
• There is a male predominance, perhaps ~2:1. (30651839)
• ~80-90% of patients are actively smoking, but ~10% of patients lack a smoking history.

non-tobacco etiologies of DIP may include: 

• Connective tissue disease:
  • Rheumatoid arthritis, especially. (26479130)
  • Lupus.
  • Scleroderma.
  • Polymyositis.
• Medications:
  • Nitrofurantoin.
  • Sirolimus.
  • Sulfasalazine.
• Infection:
  • CMV.
  • Hepatitis C.
• Myeloid neoplasms.
• Marijuana smoking. (30651839) 
• Exposures, especially inorganic dust:
  • Tool grinding.
  • Plastic machining.
  • Tire manufacture.
  • Potato chip manufacture.
  • Arc welding, solder fumes.
  • Fire extinguishing powder.
  • Metals (copper, beryllium, tungsten).
  • Mycotoxins.
  • Diesel fumes. (Shepard 2019, 26324141, 37055089, 29222007)

---

clinical findings in DIP

symptoms

• Subacute deterioration often occurs over weeks to months.
• Dyspnea is the most common symptom (85%). (37055089)
• Cough is common, usually nonproductive (65%). (37055089)
• Constitutional symptoms can occur (fevers, weight loss).

examination

• Clubbing may occur in ~50% of patients. (26324141, Walker 2019)
• Crackles are common.

---

radiology of DIP

chest radiograph

• Chest X-ray is more often abnormal in DIP (as compared to RB-ILD).
• Bilateral opacities may be noted in the middle and lower lung fields. (Murray 2022)
• Lung volumes may be reduced.

CT scan

• (1) Ground glass opacification is the primary finding (seen in all cases).
  • Distribution:
    • Usually bilateral and symmetric.
    • Tends to be peripheral.
    • Lower lung predominant.
  • However, diffuse ground glass opacities may occur. (Fishman 2023)
• (2) Microcysts (~1/3 of patients):
  • Microcysts are often clustered within areas of ground glass opacity. The presence of small cysts admixed within ground glass opacity is a unique feature of DIP (desquamative interstitial pneumonia). (31464115)
  • The etiology of these cysts is unclear. They may represent mild emphysema or early traction bronchiolectasis caused by fibrosis. (Shepard 2019) Resolution can occur over time. (27180915)
• (3) Fibrosis
  • Limited subpleural reticulation may also be seen in about half of cases. (37055089) 
  • There usually isn't severe architectural distortion or traction bronchiectasis. (26324141) However, long-term follow-up may show some honeycomb development in up to ~15% of patients. (29222007)
• Centrilobular nodules are rarely seen (unlike RB-ILD). (29222007)
• ⚠️ A confident diagnosis of DIP made by experienced thoracic radiologists was correct only 59% of the time. This reflects that the above findings are often nonspecific.

radiological differential diagnosis often focuses on:

• NSIP (both conditions may cause peripheral-predominant ground glass opacities with elements of mild fibrosis; DIP and NSIP can be radiologically indistinguishable). (Fishman 2023)
• HP (hypersensitivity pneumonitis). 📖
• Infections (e.g., pneumocystis).

---

diagnosis 

• Bronchoalveolar lavage may show eosinophilia in some cases, sometimes with moderate neutrophilia. (37055089; 29222007) As such, bronchoalveolar lavage is considered irrelevant to the diagnosis of DIP, unless it is required to exclude an alternative diagnosis. (26138798)
• Confident diagnosis generally requires a surgical biopsy or cryobiopsy. (26138798) However, if DIP is likely and the patient is stable, a diagnostic/therapeutic trial of smoking cessation with careful follow-up may be reasonable.

---

treatment & prognosis of DIP

• Avoiding the cause:
  • Smoking cessation is the fundamental intervention.
  • For DIP due to etiologies other than tobacco, avoidance or management of the underlying cause is fundamental.
• Steroid:
  • Steroid is often used, although its efficacy has not been proven. One regimen described in the literature is 40-60 mg/day prednisone for six weeks, followed by tapering off over 6-9 months. (30651839) Other authors have suggested tapering over a few weeks to months. (29222007)
  • It's unclear whether steroid causes a transient improvement, or actually alters the overall disease outcome.
  • Steroid is not recommended for patients who are continuing to smoke. (Murray 2022)
• Two cases have reported improvement following therapy with macrolide (clarithromycin). (30651839) Macrolide therapy isn't necessarily indicated, but if infection is possible, then selection of a macrolide could make sense. 
• Prognosis is generally favorable if DIP is caused by smoking and the patient is able to achieve smoking cessation. However, DIP may progress to fibrosis and mortality (especially with ongoing tobacco use).

---

questions & discussion

(back to contents)

---

To keep this page small and fast, questions & discussion about this post can be found on another page here.

Guide to emoji hyperlinks 

•  = Link to online calculator.
•  = Link to Medscape monograph about a drug.
•  = Link to IBCC section about a drug.
•  = Link to IBCC section covering that topic.
•  = Link to FOAMed site with related information.
• 📄 = Link to open-access journal article.
• = Link to supplemental media.